The antibacterial compounds tylosin and rosaramicin (5-O-(4'-deoxy-mycaminosyl)-12,13-epoxy-23-deoxy-tylonide or 5-O-desosaminyl-12,13-epoxy-23-deoxytylonide) have been utilized in the treatment of bacterial infection.
Tylosin is a 16-membered macrolide antibiotic that is characterized by two neutral sugars, one basic sugar, and, in the aglycone moiety of the molecule, by a conjugated double bond in the C-10,11 and C-12,13 positions, an aldehyde in the C-20 position and a ketone in the C-9 position. Several tylosin derivatives have been prepared. See, European Patent Application No. 0287082 to Narandja et al. and U.S. Pat. No. 4,345,069 to Sakakibara et al. It is presently believed that tylosin exerts its antibacterial action by ribosomal binding. Corcoran et al., J. Antibiot. 30:1012 (1977).
Rosaramicin is a macrolide antibiotic originally isolated from fermentations of a strain of Micromonospora rosaria. French Patent No. 2,081,448 to Weinstein et al. The structural formula for rosaramicin is similar to that of 5-O-mycaminosyl-tylonide, except for replacement of the C-12,13 double bond of the tylonide with an epoxy group and a hydroxymethylene group for the methyl of C-23, and the absence of the 4'-hydroxyl group of the mycaminosyl substituent.
The present invention relates to the production of derivative compounds having a carbon-nitrogen bond at the C-9 position, in place of the ketone moiety of rosaramicin, 5-O-mycaminosyl-tylonide and 4'-deoxy-5-O-mycaminosyl-tylonide. The present compounds exhibit superior antibiotic activity against a broad spectrum of bacterial strains.